Physiologic and behavioral changes associated with weight loss make prevention of weight regain more difficult than either initial weight loss or the prevention of weight gain. Exercise has been recommended as a critical component for the prevention of weight regain. Recommendations from the International Association for the Study of Obesity (IASO), the Institute of Medicine (IOM), and the American College of Sports Medicine (ACSM) for the prevention of weight regain range from 60-90 min/day of moderate intensity physical activity (PA). The US Department of Health and Human Services (HHS) recommends 30 min/d of moderate PA to elicit health benefits. Although not specific to weight management HSS recommendations have been interpreted to be sufficient for that purpose. Support for these recommendations is tenuous as it is derived from studies with serious flaws including: 1. cross-sectional, non-randomized observational designs; 2. randomization prior to weight loss; 3. secondary analyses of exercise groups formed at study completion; 4. self-reported levels of exercise, 5. failure to supervise exercise and verify level of exercise energy expenditure (EEEx). To date, the effectiveness of recommendations for the prevention of weight regain have not been evaluated in a properly designed and adequately powered trial. Therefore, we propose to conduct a randomized trial to: A) compare the effectiveness of the 3 exercise recommendations on the prevention of weight regain over 12 mos. subsequent to clinically significant weight loss( > 5%), and B) evaluate gender differences in weight regain in response to the 3 exercise recommendations. Secondarily we will evaluate the potential role of compensatory changes in daily PA and energy intake (EI) as mediators of weight regain in response to the 3 exercise recommendations. Participants will complete a 3 mo. weight loss intervention of decreased EI and increased EEEx (1,000 kcal/wk.), a level of exercise consistent with public health (HHS) recommendations. Participants achieving clinically significant weight loss (> 5% of initial weight), will be randomly assigned to 12 mos. of supervised exercise at levels of EEEx recommended by: 1.) HHS, ~1,000 kcal/wk., 2.) ACSM,~ 2,000 kcal/wk., 3.) IOM, ~3,000 kcal/wk. Major outcome assessments will occur prior to weight loss (-3 mos.), at completion of weight loss (0 mos.), at the midpoint ( 6-mos.), and completion of the exercise intervention (12 mos.). Assessments will include height, weight, waist circumference, maximal aerobic capacity, EI, daily PA, blood pressure and blood samples. PUBLIC HEALTH RELEVANCE: Prevention of weight regain is the greatest challenge for individuals who initially lose weight. This proposal will evaluate the effectiveness of 3 recommended levels of exercise for the prevention of weight regain and potential gender differences in this response. We will also explore the potential role of compensatory changes in daily physical activity and energy intake as factors which impact the weight regain response to the 3 levels of exercise. This information will be important in identifying the optimal exercise recommendations for both men and women as well identifying the components (i.e. energy intake or daily physical activity) that need to be emphasized and supported in weight regain prevention programs. Results from this study will provide new information relative to the use of exercise for the prevention of weight regain which could have a significant impact on reducing the prevalence of obesity in the US.